Metal oxide compositions composites thereof and method

ABSTRACT

There are disclosed amphoteric nano-sized metal oxide particles functionalized with silyl esters of a phosphonate and composites thereof with an acrylate-based monomer, including liquid crystal monomers photopolymerizable at ambient temperature. Also disclosed are the method making such functionalized particular by reacting a metal oxide with a silyl ester of a phosphonate in the presence of a non-aqueous solvent and in an inert atmosphere and the method of making the composites wherein the functionalized particles are admixed with an acrylate-based matrix monomer, including liquid crystal monomers photopolymerizable at ambient temperature. Further disclosed is the method of dental repair wherein the composites are applied to a tooth and photopolymerized.

CROSS-REFERENCES TO RELATED APPLICATIONS

The instant application is a Continuation-in-Part of U.S. ApplicationSer. No. 08/721,742, filed Sep. 27, 1996, which is aContinuation-in-Part of U.S. Application Ser. No. 08/298,836, filed Aug.31, 1994, now U.S. Pat. No. 5,670,583, which is a Division of U.S.Application Ser. No. 08/047,750, filed Apr. 13, 1993, now U.S. Pat. No.5,372,796. The entirety of the specifications and claims of theforegoing applications are specifically incorporated herein byreference.

The U.S. government has certain rights in this invention pursuant togrant number NIDCR 1 P01 DE11688.

BACKGROUND OF THE INVENTION

The instant invention relates to alkene functionalized, metal oxide,nanoparticle composites with polymerizable alkene matrix monomersprimarily suitable for dental and medical restoration; i.e., dentalrestoratives and bone repair, and to the method of their use for suchpurposes and methods of manufacture. Other applications envisionedinclude optical elements, X-ray photoresists, and repair of materials.

There have been efforts made to generate functionalized metal oxidenanoparticles to make highly uniform composite materials; namely, inU.S. Pat. No. 5,064,877 by R. Nass et al., in U.S. Pat. No. 5,030,608 byU. Schubert et al.(see also H. Schmidt and H. Wolter, J. Non. Cryst.Solids, 121, 428 (1990). They claim a method for producingfunctionalized, photopolymerizable particles by replacing groups, R, inM(R)_(n) with groups A which complex M and further contain functionalgroups which can be photopolymerized. The dispersed, individual metaloxide particles can be prepared by removing R completely, partiallyreplacing by A and then by hydrolyzing to oxide with water.Alternatively, the oxyhydroxide particles may be preformed asM(O)_(z)(OH)_(x)R_(y) and converted to M(O)_(z)(OH)_(x)A_(y) by the lossof R. The preformed oxyhydroxide is formed by Nass et al. by thehydrolysis of the organometallic M(R)_(n) by water directly or by watergenerated by reaction of acid and alcohol unlike Wellinghoff in U.S.Pat. No. 5,570,583 where the oxide is formed by direct ester exchangebetween a metal alkoxide and a strong organic acid thereby decreasingthe number of required reactants.

There have been other attempts to form organic-inorganic hybrid glasses.However, in one case a silane functionalized polymer is hydrolyzed withwater to form a network crosslinked by the resultant silica particlesmaking removal of volatile reaction products difficult [Y. Wei et al.,Chem. Mater., 2(4), 337 (1990); C. J. T. Landry et al., Polymer, 33(7),1487 (1992)]. M. Ellsworth et al. [JACS, 113(7), 2756 (1991); U.S. Pat.No. 5,412,043; U.S. Pat. No. 5,254,638] attempted to eliminate thecomposite shrinkage induced by removal of volatile reaction products byutilizing ring strained alkenoxysilanes and polymerizable solvents whereall reaction by products contribute to the SiO₂ network or the resultantinterpenetrating, matrix, organic polymer. The expected packingdisruption induced by the strained ring opening of the alkenoxysilanewas a strategy for compensating for the shrinkage induced by conversionof double bonds to single bonds Zero polymerization shrinkage is one ofthe most necessary features of a dental restorative so that accumulatedstresses do not debond the dentin-restorative interface or fracture thetooth or restorative which can result marginal leakage and microbialattack. This feature is also important in bone repair and in accuratereproduction of photolithographic imprints and optical elements.

Other attempts have been made to reduce polymerization shrinkage byutilizing nematic liquid crystal monomers. The expected lowpolymerization shrinkage for such compounds originates from the highpacking efficiency that already exists in the nematic state, thusminimizing the entropy reduction that occurs during polymerization.Liquid crystal monomers or prepolymers have another advantage in thatthe viscosity is lower than an isotropic material of the same molecularweight.

M. Aizawa et al. [JP H 5-178794, Jul. 30, 1993] disclose a bisalkenesubstituted liquid crystal crystal monomer that is suitable for dentalrestorative materials in combination with silica particle reinforcement.Latter H. Ritter [EP 0,754,675 A2] et al. also disclose liquid crystalmonomers that might be suitable for dental applications; however, inneither of the above two patents was the liquid crystal nematic at roomtemperature or dental temperature. Reactive to diluents were added tothe original compounds to generate liquid monomers and it was not clearthat liquid crystallinity was present in these mixtures. However, evenmore recently, J. Klee et al. [WO 97/14674] discuss two liquid crystalmonomers that are nematic in the desired temperature range between roomtemperature and 37° C.

Parent U.S. Application Ser. No. 08/721,742, identified above, disclosesbisalkene terminated liquid crystal monomers that form stable liquidcrystalline melts between room temperature and 37° C. and theircomposites with functionalized nanoparticles. This disclosure describesthe nanoparticles formed by the reaction of trialkylchlorosilane, formicacid and tantalum alkoxide that are quite acidic in concentratedmethanol solution and must be surface functionalized with the base,vinyl imidazole in order to neutralize the excess acidity. Thealternative functionalization with an alkene phosphate suffers from therelative hydrolytic instability of the phosphate linkage and the lowselectivity of the alkene dimethyl phosphate ester for reactor withTa—OH bonds. While very satisfactory, the composites are, however,hydrophilic, and this mitigates against their complete suitability fordental purposes.

SUMMARY OF THE INVENTION

The forgoing problems and deficiencies of the prior art are overcome bythe instant invention which provides workable oxide-monomer mixtureswith especially low polymerization shrinkage in the matrix resin whilepermitting high loading of strengthening materials and high matrixmolecular weight, and yet permitting the matrix to strain soften, andflow onto/and or into areas to be cemented, coated, or restored, such asbone and tooth crevices, and to be polymerized between −40° C. and +40°C.

Briefly, the present invention comprises novel functionalized amphotericnano-sized metal oxide particles, composites thereof, and transparent ortranslucent acrylate or methacrylate based matrix-metal oxidecompositions with photopolymerizable room temperature nematics that havehigh strength and hardness with essentially zero shrinkage.

The invention also comprises the methods of making the composites andcompositions as hereinafter set forth.

DETAILED DESCRIPTION

While the present invention can be carried out using any metal capableof forming amphoteric metal oxides to form the metal oxidenanoparticles, such as tantalum, niobium, indium, tin, titanium and thelike, it will be described in connection with tantalum. Tantalum isparticularly desired for dental and medical uses since it will provideX-ray opaque materials necessary for diagnosis by dental and medicalpersonnel.

These tantalum nanoparticles are prepared as set forth in the parentapplication identified above by ester exchange of tantalum oxide with anacid such as formic acid.

For this invention it is important that such nanoparticles benon-interacting without high surface acidity which is detrimental fordental applications, especially. In addition, it is preferable that thealkene be reacted with the oxide surface through a phosphonate linkagewhich has good hydrolytic stability and will react with Ta—OH bonds onlythrough the ester bonds. In order to make an especially activephosphonating species we reacted the dimethyl ester of the methacrylphosphonate with a silanating agent to form the hydrolytically unstablevinyl dimethyl silyl ester. The silanating agent can be a chloride, asshown below, or a bromide.

This reaction is quite generic and can be utilized to form the anytrialkylsilyl ester (for example, trimethylsilyl) of any functionalizedphosphonate, including vinyl phosphonate. Suitable esters have thegeneral formula:

wherein R is a photopolymerizable group, such as a vinyl, acryl, ormethacryl group, and R′, R″, and R″′, which can be the same ordifferent, are an alkyl or alkene group.

For purposes of further illustration, in addition to the trialkylsilylester of vinyl phosphonate, phosphonates having the following groups canalso be used:

1. R is —CH═CH₂ and R′, R″, and R″′ are each —CH₃;

2. R is

and R′, R″, and R″′ are each —CH₃; and

3. R is

and R′, R″, and R″′ are each —CH₃; and R″′ is —CH₂═CH₂

The silyl phosphonate ester can serve two purposes: one as a surfacephosphonating agent and the other as a surface silanating agent whichwill generate the hydrophobic surface necessary for incorporation intohydrophobic monomers. If the silane is alkene functionalized it willphotopolymerize and immobilize into the matrix monomer, eliminating anypossibility of migration out of the composite which could adverselyaffect the mechanical properties, such as shrinkage.

This reagent is conveniently incorporated into the preparation as setforth in the parent application identified above by ester exchange oftantalum ethoxide with an acid such as formic acid. Even thoughextensive phosphonating and silation of the tantalum oxyhydroxide takeplace the infrared spectrum still indicates a substantial amount ofuncondensed Ta—OH to be present.

The remaining accessible Ta—OH can be further reduced by the addition ofa trifunctional silane such as 3-(trimethoxysilyl) propyl methacrylateto the formic acid mixture. This component is also of use since themultiple Ta—O—Si bonds formed by the trifunctional silane are morehydrolytically stable than the monofunctional silanes. In addition, thesilane effectively blocks access to unreacted Ta—OH bonds. Thus,interparticle hydrogen bonding associations between Ta—OH bonds onadjacent particles is blocked and premature phase separation of atantalum rich phase in the hydrophobic matrix monomer is avoided.

Alternatively, the tantalum oxide can be prepared as in the parentapplication with the silyl phosphonate and trifunctional silanesubsequently added to an alcohol solution of the tantalum oxidenanoparticles.

These tantalum oxide nano-sized particles (nanoparticles) form highlyacidic (pH=2-3) solutions in alcohols most probably due to absorbedacid. This is first removed by exposing the oxide solution to acrosslinked gel of poly 4-vinyl pyridine which increases the pH to 6, avalue suitable for further composite manufacture. The particle size isnot critical, with about 150° A being a desirable size and over 100° Abeing suitable.

A 10-30 wt % solution of tantalum oxide nanoparticles is then mixed witha solution of a matrix monomer which may be glycerol monomethacrylate,glycerol dimethacrylate, hydroxyethylmethacrylate (HEMA),2,2-bis[p-(2′-hydroxy-3′-methacryloxypropoxy)phenylene] propane(Bis-GMA), or ethoxylated bis-GMA and various blends of these monomersin combination with known plasticizers, such as trithethyleneglycoldimethacrylate, and polypropylene oxide monomethacrylate and knownphotoinitiators such as camphorquinone and and photoactivators such as2-n-butoxyethyl-4-(dimethylamino)benzoate.

After evaporation of the solvent under high vacuum at room temperature,a clear fluid mixture of the tantalum oxide and the matrix monomer isformed which can be cast into molds or coated onto substrates andphotocured into a glassy transparent solid.

Composite fluids containing the more hydrophilic monomers are morestable to phase separation into a clear gel which probably containsinterpenetrating tantalum rich and tantalum poor phases of such a smallsize scale (<3000 A) that light scattering is minimized. Nanoparticleswhich are relatively more hydrophobic due to a more extensive reactionwith the phosphonating or silanating reagents are also stable to phaseseparation in hydrophobic monomers.

For many applications which include biomedical repair, the curedcomposite must be resistant to swelling by saline solution at 37° C. Forthis reason matrix monomer blends containing high concentrations ofhydrophobic monomers like ethoxylated bis-GMA are to be preferred overthose containing hydrophilic monomers such as HEMA. Surface swelling bysaline results in surface solvent crazing which can be deleterious tothe physical strength of the composite.

Parent U.S. Application Ser. No. 08/721,742 noted above describes theuse of bis acrylate and methacrylate terminated liquid crystals whichare especially useful as matrix monomers.

As to the matrix monomers there are used photopolymerizable, acrylatebased monomers particularly those useful in dental applications.Particularly preferred are the bisacrylate terminated nematic liquidcrystals having the formula:

In this formula_(n) is a C₆ to C₁₂ substituted or unsubstituted alkylgroup, R₁ and R₃ are H or a methyl group and R₂ is a bulky group (agroup capable of providing steric hindrance), such as a tertiary butylgroup and the like. This large group size “mismatch” between the centralaromatic group and the two surrounding aromatic groups is required toachieve in the final product a nematic state at room temperature whilesuppressing crystallinity at the same temperature.

The methacrylate derivatives of the above diacrylates are also suitable.Also, as discussed below, bis-GMA and other bis-glycidylacrylate andmethacrylate compounds can be induced in the matrix. Of special interestare bis-(4-(6-acrylolyloxyhexyl-1-oxy)benzoyl)2-(t-butyl) quinone(C6(H,TB,H)and bis-(4-(10-acrylolyloxydecyl-1-oxy)benzoyl)2-(t-butyl)quinone (C10(H,TB,H) both of which are nematic liquid crystals betweenroom temperature and 40° C. In addition to the hexyl and decyl groups itis possible to make suitable nematic liquid crystals utilizing otheroligoethylene groups such as heptyl, octyl, and nonyl groups. Althoughmolecules of this general structure have been synthesized, practicalapplication in low polymerization shrinkage applications was precludedbecause of the development of crystallinity at room temperature whicheffectively prevents manipulation of the material. However, the novelsubstitution of the central aromatic group with an especially bulkygroup such as t-butyl was found to suppress crystallinity at roomtemperature while still permitting the nematic state to exist. Bothcould be photopolymerized to about 2% linear polymerization shrinkage(5.9% volumetric shrinkage) at about 50% double bond conversion; thisvolumetric shrinkage is more than 2.6× less than typical commercial,unfilled resins. Addition of filler should be able to reduce thissubstantially because of the volume filling effect.

Even though C6(H,TB,H) of purities less than 95% can't crystallize fromthe melt, material purified to 99+% by column chromatography could bevery slowly crystallized from methanol and diethyl ether to produce asolid that melted at 67° C. Once melted, however, the material would notrecrystallize in the absence of solvent. The expensive column separationcould bc avoided by seeding the crude liquid crystal in methanolsuspension at −20° C. with the column prepared crystals. The observationthat the crude material can be solvent crystallized, but not meltcrystallized is an important since it provides a cheaperrecrystallization route to purification that might not rely on expensivecolumn separation and, in addition, the desirable stability of theliquid crystalline state to premature crystallization and solidificationat room temperature is maintained.

The purified C6(H,TB,H) underwent a combined smectic or nematic toisotropic transformation at 43° C. which is above the mouth temperatureof 37° C., thus making it useful for polymerization out of the liquidcrystalline state. A glass transition appeared at −40° C.

C6(H,TB,H) of only 90% purity (crude), and 95% purity (semicrude),respectively, either never crystallized or crystallized even more slowlyto a lower melting, partially crystalline material (melting point=60°C.). In addition the smectic to isotropic and nematic to isotropictransition temperatures diverged, now changing to T_(s−>n)=25° C.,T_(n−>isotropic)=42° C. for the semicrude material and T_(n−>)=18° C.,T_(n−>isotropic)=40° C. The major impurity in this material seemed to bea hydrochlorinated derivative of C6(H,TB,H), HC 1 (e.g. CH₂Cl—CH₂—C(O)—)that was generated in the acrylolyation step and was impossible toseparate by column chromatography and showed a strong tendency tococrystallize with C6(H,TB,H). It's immediate effect was to completelyinhibit the ability of the C6(H,TB,H) to melt crystallize; however, nosuppression of the T_(n−>isotropic) was noted up to at least 14% ofC6(H,TB,H),HC 1. Thus a clear strategy for retarding crystallizationbesides including a t-butyl group on the central aromatic ring is to mixliquid crystal having different end groups but the same t-butylsubstituted central aromatic structure.

The importance of the above result is that considerable amounts ofsoluble impurity can be added to the liquid crystalline material withoutchanging its T_(nematic−>isotropic) transition temperature. Thus, a highvolume fraction of tantalum oxide or silicon-tantalum oxidenanoparticles (semisoluble “impurity”)can be added to the liquid crystaland the resultant composite can maintain the desirable, low viscosityflow and low polymerization shrinkage characteristics of the continuousliquid crystal matrix at room temperature up to dental use temperatures.

Highly purified C6(H,TB,H) can be codissolved with at least 30wt %tantalum oxide nanoparticles in a variety of solvents to make clearsolutions. Once the solvent is pumped off a translucent pasty fluid isgenerated which contains partially crystallized C6(H,TB,H) nucleated bythe tantalum oxide phase. These monomer crystals can be melted at 60° C.and a clear isotropic to melt can be obtained down to 42° C. at whichtemperature the nematic phase is formed. This thermotropic transition isfully reversible. After an extended period; however, the C6(H,TB,H) willrecrystallize. The crystallization can be avoided if melts containingmore than about 5% of C6(H,TB,H), HC 1 are employed.

The compositions are prepared by mixing functionalized metal oxidenanoparticles with a photo or thermally polymerizable matrix monomer orprepolymer. The specific non-aqueous method of producing the oxideparticles permits alkene functionalized (R) phosphonates and silanes tobe bound to the metal oxide through —(M—O)₂—P(O)—R,—(M—O)_(4-x)Si(R)_(x), x=1-3 linkages. The functionalized metal oxideparticle is formed when activated molecules such as silyl phosphonates[CH₂═CH—Si(Me)₂—O]₂—P(O)R or (MeO)_(4-x)Si(R)_(x) condense with M—OHbonds formed during the synthesis of the metal oxide nanoparticles. Thesilyl phosphonate is unique in that it will not only phosphate thesurface but will also generate a silanol in situ which will silanate thesurface of the nanoparticle. Metal phosphonate bonds are advantageoussince they are more hydrolytically stable than metal silanol bonds.

The hydrophobicity of the nanoparticle can be increased by increasingthe number of functionalized M—OH bonds. The ability to alter thesurface of the nanoparticle in a controlled way permits control of theworking time of the unpolymerized composite and modification of thefinal cured microphase structure of the composite material.

For example if a hydrophobic, matrix monomer and hydrophilicnanoparticles are dissolved in a common hydrophilic solvent evaporationof the solvent will yield an initially mobile fluid which will rapidlyphase separate to form an elastic gel. Elastic properties are generatedby an interpenetrating network phase of hydrophilic metal oxidenanoparticles within the hydrophobic matrix. If on the other handhydrophobic, matrix monomer and relatively hydrophobic nanoparticles aremixed in a common solvent and the solvent is evaporated, microphaseseparation will proceed more slowly providing increased working orstorage time in the mobile state. With increased working time thekinetic development of phase separation can be terminated at differentstages by polymerization of the matrix monomer or prepolymer.Interconnectedness of the oxide network can have a strong influence onmechanical, permeability and electrical conductivity of the material.

By appropriate matching of the surface properties of the nanoparticlesand the matrix monomer it is possible to make a one phase system orgenerate a very fine phase separation that is insufficient to scatterlight. This is of specific importance in many applications since theability to uniformly photocure several millimeter thicknesses ofmaterial to a solid is rendered. In addition, opacifying particles canbe added to the transparent base for better control of cosmeticfeatures.

The invention will be further described in connection with the followingexamples which are set forth for purposes of illustration only.

EXAMPLE 1 Tantalum Oxide Nanoparticle Synthesis

(a). Chlorotrimethylsilane (4.0019 g, 0.0368 mol), tantalum ethoxide(30,4454 g, 0.0749 mole), a-bis(trimethylsilyl) vinylphosphonate (3.9994g, 0.0158 mol) and formic acid (7.1262 gm 0.1548 mol) were added in theabove sequence under nitrogen while stiring at room temperature for 7hrs (did not gel) before pumped vacuum for 20.5 hrs to give a whitepowder. The powder dissolved in methanol in two hours at 10 wt %concentration, the pH of the solution was about 2.

(b). Chlorotrimethylsilane (7.15 g. 0.0658 mol), tantalum ethoxide(56.09 g, 0.138 mole), 2-bis(trimethylsilyl)phosphonoethyl methacrylate(8.56 g, 0.0253 mol) and formic acid (13.16 g, 0.286 mol) were added inthe written sequence under nitrogen with stirring 30° C. bath for 7.5 hr(it gelled at about 6 hrs). After vacuum pumping for 29 hrs, whitepowder was obtained. The powder dissolved in methanol in about two hoursat 10 wt % concentration; the pH of the solution was about 2.

(c). Tantalum ethoxide (0.9707 g, 0.00239 mol),chlorovinyldimethylsilane (0.1194 g, 0.000990 mol),3-(trimethylsily)propyl methacrylate (0.2056 g, 0.000828 mol) and formicacid (0.2026 g, 0.00440 mol) were added in the written sequence undernitrogen while being stirred. The resulting clear liquid turned viscousand eventually gelled in about 0.5 hr. The reaction mixture was left atroom temperature for 17.5 hrs before being vacuum pumped for 8 hrs togive a white powder. The product dissolved in methanol at roomtemperature in one hour at 10 wt % concentration; the pH of the solutionwas about 3 to 4.

EXAMPLE 2 Tantalum Oxide Nanoparticle-Isotropic Hydrophobic MonomerGlasses

(a). 1.0187 g of the tantalum oxide methanol solution [9.5 wt %,neutralized with poly(4-vinylpyridine)] and 0.1970 g2-hydroxylethylmethacrylate (HEMA) were mixed; the resulting clearsolution was pumped under high vacuum. After complete evaporation ofmethanol and a small amount of HEMA, a clear liquid was obtained whichcontained 35 wt % tantalum oxide. The liquid gelled in 30 mins.

(b)(i). 1.2901 g of the tantalum oxide methanol solution [10.1 wt %;neutralized with poly(4-vinylpyridine)] and 0.4033 g HEMA were mixed;the resulting clear solution pumped under high vacuum. After completeevaporattion of methanol and a small amount of HEMA, a clear liquid wasobtained which contained 29.6 wt % tantalum oxide. The liquid gelleddays later.

(ii). 6.2518 g of the tantalum oxide methanol solution [8.7 wt %;neutralized with poly94-vinylpyridine)], 1.2835 g glyceroldimethacrylate and 0.0073 g camphorquinone were mixed; the resultingclear yellow solution was pumped under high vacuum. After the completeevaporation of methanol, a clear yellow liquid resulted; after additionof 0.0078 g dimethylaminoethyl methacrylate, the liquid was photocuredfor 3 mins each side and transparent, slightly yellow composite wasobtained. This composite contains 29.6 wt % of tantalum oxide. The pointbending specimen showed solvent stress crasing after prolonged exposureto saline solution at 37° C.

(iii). In the following examples, neutralized tantalum oxide methanolsolution was first reacted with a silane compount[vinylethoxydimethylsilane, chlorovinyldimethylsilane,ethoxytrimethylsilane or 3-(trimethoxysily)propyl methacrylate] atelevated temperature before the addition of monomers. The resultingclear solutions were vacuum pumped as detailed in the following table.

Reaction time (hr) and temperature No Reagent (° C.) Composition andresults 1 Ta₂O₅/CH₃OH (9.97%) 1.5085 g 1.5 hr; 55-56 Ta₂O₅ 0.1504 g(22.9%) ethoxytrimethylsilane 0.5 mL PPGMMA 0.5065 g (77.1%) clearliquid for at least 26 hrs at RT 2 Ta₂O₅/CH₃OH (9.97%) 1.6450 g 2.0 hr;53 Ta₂O₅ 0.1640 g (29.6%) ethoxytrimethylsilane 0.6 mL PPGMMA 0.3898 g(70.4%) clear liquid for at least 1.8 hrs at RT 3 Ta₂O₅/CH₃OH (9.97%)1.5 mL 5.4 hr; 53 Ta₂O₅ 0.12 g (19%) ethoxytrimethylsilane 0.5 mL PPGMMA0.3536 g (55.6%) unity cement 0.1621 g (25.4%) small amount of liquidspread on the wall of RBF (gelled at bottom) which gelled within 16.8 hr4 Ta₂O₅/CH₃OH (10.89%) 8.1764 g 48 hr; 52 (A)Ta₂O₅ 0.4473 g (30.1%)ethoxytrimethylsilane 10.0 mL unity cement 1.0372 g (69.9%) very viscousclear liquid which gelled within 3.5 hr at RT; photocured 60s to a hard,transparent specimen (B)Ta₂O₅ 0.4253 g (29.9%) UDMA 0.9985 g (70.1%)clear sticky gel resulted; photocured 60s to a hard, slightly hazyspecimen 5 Ta₂O₅/CH₃OH (10.89%) 1.6724 g 3.3 hr; 55-58 Ta₂O₅ 0.0578 g(26.3%) vinylethoxytdimethylsilane 0.6 mL PPGMMA 0.1622 g (73.7%) clearliquid for at least 17.2 hr stored at RT 6 Ta₂O₅/CH₃OH (10.89%) 1.7900 g4.4 hr; 50-55 Ta₂O₅ 0.1949 g (16.3%) TMSPMA 0.5 mL TMSPMA 0.52 g (43.3%)PPGMMA 0.4836 g (40.4%) clear liquid for more than a month at RT 7Ta₂O₅/CH₃OH (10.89%) 4.5434 g 26.3 hr; 51-53 Ta₂O₅ 0.4689 g (30.1%)TMSPMA 0.5 mL TMSPMA 0.4589 g (29.4%) unity cement 0.6311 g (40.5%)viscous clear liquid for at least 1 hr at RT; photocured 60s to a hard,transparent specimen (w/bubbles) 8 Ta₂O₅/CH₃OH (10.89%) 1.0603 g 15.8;53 Ta₂O₅ 0.1155 g (28.2%) chlorovinyldimethylsilane 1.0 mL unity cement0.2940 g (71.8%) yellow liquid for at least 30 hr at RT; photocured 120sto a hard, transparent specimen PPGMMA—polypropylene glycolmonomethacrylate (Polysciences, Mw 360-390) RBF—round bottom flask

(c) The above reaction was scaled up to three times and used to preparesamples from three point bending tests as detailed in the following.1.4341 g of the tantalum oxide powder was dissolved in 11.08 g methanolfollowed by neutralization with 0.2246 g lightly crosslinkedpoly94-vinylpyridine). After centrifuging to remove thepoly94-vinylpyridine), the supernatent methanol solution of tantalumoxide with a pH of about 6 was then reacted with 4.5 mLvinylethoxydimethylsilane at about 50° C. for 24 hours before theaddition of 3.01 g matrix monomer resin followed by evaporation ofsolvent and excess vinylethoxydimethylsilane under high vacuum. Thematrix monomer utilized was the hydrophobic, photopolymerizable Unitycement (Coltene).

A clear yellow free flowing liquid resulted when all the solvent wasremoved. The liquid was put into transparent silicone, three pointbending molds and photocured with blue light from a dental curing lampfor 60s from both top and bottom side to give transparent, slightlyyellow samples. The final composition was 30 wt % tantalum oxidenanoparticles and 70% matrix monomer.

The three point bending fracture strength of nanoparticle composite wascompared with Unity cement and a Unity cement containing 70 wt %microfiller is compared in FIG. 1 after soaking for 24 hrs in salinesolution at 37° C.; none of the samples showed any evidence of stresscrazing. Although the transparent nanoparticle composite is weaker thanthe opaque microfilled Unity cement and the unfilled unity cement, ithas the advantages of optical transparency, more univorm photocure, andradioopacity.

The three point bending results are shown in the following tables:

Material Flexural Strength Pure UC 15,271.66 Filled UC 18,658.58 Ta2O5 7,482.17 t-Test: Two-Sample Assuming Unequal Variances Pure UC FilledUC Mean 15271.656 18658.58225 Variance 2876336.2 4778286.125Observations 9 11 Hypothesized Mean Difference 0 df 18 t Stat −3.900544P (T <= t) one-tail 0.0005241 t Critical one-tail 1.7340631 P (T <= t)two-tail 0.0010481 t Critical two-tail 2.1009237 t-Test: Two-SampleAssuming Unequal Variances Pure UC Ta2O5 Mean 15271.656 7482.166873Variance 2876336.2 1411017.661 Observations 9 13 Hypothesized MeanDifference 0 df 13 t Stat 11.904735 P (T <= t) one-tail 1.15E−08 tCritical one-tail 1.7709317 P (T <= t) two-tail 2.299E−08 t Criticaltwo-tail 2.1603682

EXAMPLE 3 Synthesis and Purification of Liquid Crystal Monomers

A. The initial step comprises reacting the compounts set forth in thetable below.

Ethyl-4- Hydroxy- Potassium 6-Chloro- Sodium Compound Benzoate Hydroxide1-Hexanol Iodide C6 Equivalents 1 1.2 1.2 1.4 1 Formula 166.177 56.11136.62 149.89 238.28 Weight Millimoles 609.96 731.96 731.96 853.94609.93 Mass 101.36 41.07 100 127.99 145.33

The reaction is as follows:

A flame dried 2 liter, three neck round bottom flask was outfitted witha water cooled condenser and stir bar and cooled under house nitrogen.To this was added 101.36 grams (610.0 mmol) of ethyl-4-hydroxy benzoate(99%, Acros 15025-0010), 500 milliliters of acetone (Fisher Optima, usedas received only from a fresh bottle) and 41.07 (732.0 mmol) ofpotassium hydroxide (ACS Certified, Fisher Scientific P250-500). Thiswas stirred until the potassium hydroxide dissolved entirely, producinga small amount of clear oil on the walls of the flask. The reaction wasmildly exothermic, the flask becoming warm to the touch as the KOHdissolved. Heat may help speed the dissolution of the KOH, but this wasnot necessary. At room temperature, 100 grams (732 mmol) of6-chloro-1-hexanol (95%, Acros10928-1000) and 128 grams (854 mmol) ofsodium iodide (Anhydrous, 99+%, Acros 20318-0010) were added to producea clear solution with a dispersed white solid. The white solid caninterfere with the stir bar, and unless a really good stir plate andstir bar were used, mechanical stirring was needed. An additional 500 mlof acetone was added. The acetone was added in two aliquots because itcomes in 500 ml bottles and thus the walls of the flask and the funnelscan be rinsed down with each addition of reagents. This is heated toreflux for 24 to 48 hours. As the reaction reaches completion, a largeamount of waxy tan precipitate lines the walls of the flask. The besttest for completion, however, is to monitor the reaction by TLC forsignificant disappearance of the starting materials.

A convenient spot test for 6-chloro-1-hexanol, which does not show up byfluorescence or iodine, is to immerse the TLC plate in a solutioncontaining 4 ml of concentrated sulfuric acid in 100 ml of methanol. TheTLC plate is heated to 200° C. on a glass plate and a charred brown spotappears. Only the product and 6-chloro-1-hexanol are charred withsulfuric acid.

TLC of the reaction mixture in ether on a silica gel plate shows UVactive spots at RF=0.72, 0.62, 0.45, 0.29, 0.18, and 0.00 and spots thatwere charred with sulfuric acid at RF=0.53 and 0.45. The largest spot,which corresponds to the ethanol ester of the product appears at RF=0.45and is observable with UV and the sulfuric acid stain. The product spotoverlaps the acid charred spot at RF=0.53 which corresponds to6-chloro-1-hexanol. However, they remained distinct, even whenadditional 6-chloro-1-hexanol is spotted with the product. A smallamount of 6-chloro-1-hexanol and ethyl-4-hydroxy benzoate (RF=0.62) areevident in the reaction mixture.

After significant disappearance of the starting material was observed,the solution was filtered by gravity. The filtrate and the waxyprecipitate lining the flask walls were dissolved in water and a smallamount of ether. It appeared to be a salt dispersed in insoluble organicmaterial, as it did not dissolve fully until the ether was added. Thesupernatant acetone was removed in vacuo at 60° C. and the residue wasdissolved in ether and a small amount of water. The two were thenrecombined in a separatory funnel and the aqueous phase extracted threetimes with ether. This process of separating and recombining the solidand liquid phases of the reaction ensures all solids are fully dissolvedand helps avoid serious emulsions during the extraction.

Ether was removed in vacuo, and the residue was refluxed with an aqueoussolution containing 34 grams of sodium hydroxide (855 mmol) for 4 to 12hours. Typically, the solution was diluted with water to make a totalvolume of 500 to 800 ml. This produced a yellow solution containing thesodium salt of our product, along with residual starting materials. Theaqueous solution of the sodium salt is only meta-stable, and the saltcan precipitate if cooled in ice or allowed to stand for a few hours atroom temperature. Addition of more water (possibly diluting up to 3liters) along with slight warming can help redissolve the precipitate.

The solution was extracted three times with ether to remove residualstarting material. The aqueous phase was then titrated to a pH of 3 with6N HCl, forming a white precipitate. The mixture is filtered and thesolid recrystallized from isopropanol and washed with hexanes.

On one occasion, I forgot the second extraction and titrated the aqueoussolution directly after the saponification reaction. There was still alot of 6-chloro-1-hexanol present (identified by smell) after the firstrecrystallization, but a second recrystallization from IPA removed itentirely (verified by NMR and melting point). This could possibly be thebest method, because the product can be precipitated from the hotaqueous solution, well before crystals of the sodium salt have a chanceto grow. I have duplicated this method, and the yield is comparable tothat when the saponified product is extracted with ether.

At times it has been difficult to recrystallize the product, especiallyif the sodium salt has precipitated from solution. Not all of thematerial would dissolve in boiling IPA, and hot filtration seemed tohave no effect. Some powder was retained on the paper, but crystals thatformed in the receiving flask as the filtrate cooled were even moredifficult to dissolve. It is possible that small amounts of the sodiumsalt are responsible. This problem has appeared intermittently, bothwhen the saponified product was extracted with ether, and the etherextraction step was skipped.

The reaction yields ranged from 100-114 grams (68-78%)

B. Second Step-Acryloylation

Acryloyl C6- Compound C6 DMA Chloride Acr Equivalents 1 1.3 1.15 1Formula Weight 238.28 121.18 90.51 329.02 Millimoles 329.02 427.7 378.4329.02 Mass (g) 78.4 51.83 34.25 96.18

The reaction is as follows:

This is a troublesome reaction, in which a hydrochlorinated impurityappears. The general reaction scheme involves the reaction of C6 withacryloyl chloride in the presence of a base or catalyst.

In a generalized procedure, 31.4 grams of C-6 (132 mmol) was dissolvedin 500 ml THF at 60 EC. Dimethyl aniline (171 mmol) was added bypipette. Freshly distilled acryloyl-chloride was added by pipette (150mmol) drop-wise. This produced a white precipitate and caused a somewhatvigorous exothermic reaction. The solution was stirred for 24-48 hoursuntil substantial amount of the starting material has disappeared asevident by TLC in ether. The starting material has a UV fluorescenceinhibiting spot at RF=0.26. The product has a UV fluorescence inhibitingspot at RF=0.50. There are other less significant fluorescenceinhibiting spots of unknown origin (suspected acryloyl anhydride ofproduct and starting material respectively) at RF=0.56 and RF=0.33.

After the reaction is finished, THF was removed in vacuo and the residuewas partitioned between methylene chloride and water. The organic phasewas extracted three times with water (very gently to avoid emulsion) andeach time the aqueous pH is reduced to 3 to help remove amines. Theorganic phase was collected, dried in vacuo, and the residuerecrystallized from isopropanol. (Yield=85-90%).

There are two coupled triplets in the proton NMR spectrum at 2.9 and 3.9ppm. These are most likely the product of HCl addition across the doublebond, forming a 3-chloro-propionate. NMR simulations corroborate thishypothesis. Relative concentrations of the 3-chloro-propionate impuritywere estimated by comparing the integration value of the impurity peakswith the value of the allyl protons in the spectrum. The productcontains approximately 8 to 10% impurity when synthesized in THF.Amounts can range from 0-4% when synthesized in chloroform to 20-25%when synthesized in THF without a base. Our referred method is to usechloroform as a solvent although the yield is low (48%).

Variations include:

Chloroform Our C-6 starting material was barely soluble. C6,Dimethylaniline, and acryloyl chloride were added to chloroform (FisherOptima, used as received and stored under nitrogen) at room temperatureand heated to reflux. (10 ml of chloroform for each 1 g of startingmaterial C6) After 12 hours, most of the powder has dissolved, forming aslightly cloudy solution. The starting material was mostly gone by TLC.After recrystallization, NMR shows that the chloropropionate impurityhas been reduced to 0-4%.

Pyridine

The use of pyridine as the base or a combination of pyridine anddimethylaminopyridine catalyst has produced a low yield in everyinstance. The impurity is still present when pyridine and THF are usedtogether. The reaction of acryloyl chloride is more vigorous than withdimethyl-aniline and caution should be used when it is added. Additionof 15% excess acryloyl chloride produced an incomplete reaction asobserved by TLC. Addition of 100% excess acryloyl chloride removes thestarting material, but isolated yields are still low. This is true forusing pyridine in a variety of solvents and using pyridine as thesolvent.

Dioxane

Our C-6 starting material was added to dioxane (10 ml for every gram)and heated to 60 EC to produce an inhomogenous mixture. Dimethyl anilinewas added. Acryloyl chloride was added dropwise (nothing excitinghappens, but the solution clears). Reaction products include our the3-chloropropionate impurity, and an additional impurity with similar NMRshifts.

The best way to work the reaction up is to add one aliquot of bothmethylene chloride and water (i.e. 50 ml of DCM and 50 ml of water to 50ml of dioxane) to the reaction solvent, and to extract the organic phasethree times with water, removing most of the dioxane as well as anyamines.

t-butyl- hydro- Compound C6-Acr quinone TEA MeSO2Cl DMAP Equivalents 2 14.2 2.1 0.2 Formula Weight 292.33 166.22 101.19 114.55 122.17 Density0.726 1.48 Millimoles 269.5 134.8 566 283 26.95 Amount 78.8 g 22.4 g78.9 ml 21.9 ml 3.29 g

The reaction is as follows:

C6-Acr was dissolved in freshly distilled, anhydrous THF (20 ml/gram)and cooled in a dry ice/acetone bath, forming a clear yellow solution.TEA and Methane-sulfonyl-chloride were added, forming a cloudy yellowsolution. This was allowed to stir for 1 hour, and t-butylhydroquinoneand dimethylaminopyridine were added. This was warmed to 0° C. andstirred overnight, warming to room temperature as the ice in the coolingbath melts. The white precipitate was filtered by gravity, and theresultant yellow solution partitioned between ethylene chloride andwater. The aqueous phase was titrated to pH=2 (measured after stirring)and the organic phase was collected and extracted two more times withwater. Sometimes it was necessary to add a half saturated NaCl solutionto avoid emulsions. It is helpful to stir the extractions gently, asopposed to shaking to avoid emulsions.

Chloroform was removed in vacuo, and the resultant paste is purified byeither liquid chromatography or recrystallization.

Yield is about 70 ml of crude product, but only a few grams afterpurification.

D. Liquid Chromatography

Samples of the C6-LX were purified by liquid chromatography over silicagel using 1:1 (v:v) solution of hexanes and ethyl ether. The silica gelpurchased from Aldrich (stock number 28,859-4) was 200-400 mesh, 60angstrom with a BET surface area of 500 m²/g and a pore volume of 0.75cm³/g. The size of the silica column was 50 mm diameter by 33 cm length.Ether was added to our sample until it could be transferred by pipette,and it was added to the column to produce a 2 mm tall band (about 4 ml).Three 100 ml fractions were collected, followed by 9 ml fractions. PureC6-LX eluted between about 950 ml and 1400 ml of solvent eluted(including the fore-fractions). The solvent was removed in vacuo and theresulting oil recrystallized by dissolving in about 3 ml of ether andplacing in the freezer (−10 EC). About 500 mg of pure compound wasisolated for each column run. There is a substantial amount of materialat the top of the column (RF=0) which appears to be polymerized product.This indicates that further precautions should be taken to preventpolymerization. The procedure yields about 15% pure C6-LX, compared tothe amount of crude material loaded on the column.

E. Recrystallizing C10-LX

After the coupling reaction, 25 ml of crude material was dissolved inmethylene chloride and gently extracted (no shaking to avoid emulsion)three times with dilute HCl (pH=4). The methylene chloride was removedin vacuo at 30 degrees and the sample was washed into boiling methanolto produce a cloudy liquid. As the mixture cooled to room temperature, abrown oil collected on the bottom of the flask. The mixture was wrappedin aluminum foil and allowed to sit for three days at room temperature.It was then moved to the refrigerator at about 5 degrees where is satfor another two days. Finally, it was moved into the freezer at about−10 degrees, and a yellowish white solid formed in the bottom of theflask. TLC shows the solid is remarkably enriched with the top 2 TLCspots, whereas the liquid contained almost entirely the lower spots ofthe crude reaction mixture. After melting, the solid was liquidcrystalline at room temperature.

The solid was again washed with hot methanol and placed in therefrigerator. After 3 days, several small white crystals formed on thewalls of the flask. The crystals continued to grow for about two days,after which the brown oil precipitated as a yellowish white solid. Thewhite crystals from the walls of the flask had a melting point of 37-38EC. The yellowish solid from the bottom melted to a liquid crystal atroom temperature. TLC showed only the top spot (RF=0.34), and NMR showedno difference in purity between the two. The chloropropionate impurity,which is evident only by NMR, was present in the same concentration inboth samples.

In an attempt to remove the impurity, a small sample of the whitecrystals was dissolved in ether, and a portion was passed through asilica gel pipet column. A second portion was passed through a column ofAldrich Acidic Alumina. NMR showed a slight decrease in the impurityconcentration (maybe as much as 10%), but no strong cleaning effect.

After decanting the methanol, the white crystals and brownish liquidcrystal were allowed to sit at room temperature in the dark of one week.TLC revealed additional spots, in smaller concentrations at RF=0.30 andRF=0.24. Furthermore, a weakly UV active streak continued from thelowest spot to the baseline. These seem to indicate slow polymerizationof the material.

EXAMPLE 4 Tantalum Oxide Nanoparticle-Liquid Crystal Monomer Composites

(1) Recrystalized liquid crystal monomer (C6) 0.0062 g in 0.42 g ethylether and 8.5 wt % tantalum oxide methanol solution [(from example 1,No. 3) were mixed to a slightly couldy solution and neutralized withpoly(4-vinylpyridine)]. The solution was deposited onto a microscopeslide and after the evaporation of solvent a white opaque paste resulted(The composite contained 30.5 wt % tantalum oxide). Optical microscopyunder crossed polarizers revealed that some crystallization (Tm=60° C.)had occurred; however, when, the sample was melted and cooled areversible T_(n−>i) phase transition was seen at ca. 40° C. The sampledid not crystallize upon standing at room temperature.

(2). Crude liquid crystal monomer C6(H,TB,H), 15% hydrochlorinationimpurity) 0.0342 g in 0.37 g 2-methoxy ethyl ether and 8.5 wt % tantalumoxide methanol solution [(from example 1, No. 3) were mixed to a clearsolution and neutralized with poly(4-vinylpyridine)] were mixed to aclear solution. The solution was deposited onto a microscope slide andpumped dry under high vacuum. A translucent white paste was obtainedafter the evaporation of solvent. (The resulting composite contained30.9 wt % tantalum oxide). Optical microscopy under crossed polarizersrevealed that some crystallization (Tm=60° C.) had occurred; however,when, the sample was melted and cooled a reversible T_(n−>) _(i) phasetransition was seen at ca. 40° C. The sample did not crystallize uponstanding at room temperature.

(3) Crude liquid crystal monomer, C6(H,TB,H), 15% hydrochlorinationimpurity), 0.1982 g dissolved in 1.75 g ethyl ether was added slowly to1.0040 g 8.5 wt % tantalum oxide mthanol solution [(from example 1, No.3); neutralized with poly(4-vinylpyridine)] with 0.0011 g camphorquinoneand 0.0011 g ethyl-4-dimethylaminobenzoate. The resulting solution wasslightly cloudy. The solution was deposited in a mold and the solventevaporated under vacuum. A sticky, yellow paste was formed with wasphotocured with a blue light dental curing lamp for 60s to give a hard,light yellow opaque specimen (The composite contained 30.2% tantalumoxide).

While the invention has been described in connection with a preferredembodiment, it is not intended to limit the scope of the invention tothe particular form set forth, but on the contrary, it is intended tocover such alternatives, modifications, and equivalents as may beincluded within the spirit and scope of the invention as defined by theappended claims.

What is claimed is:
 1. Liquid crystal monomers comprising bis(4-(6-acryloyloxy-A-1-oxy)benzoyl)2-(t-butyl) quinone in which A is selected from the group consisting of a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, or a mixture of such monomers.
 2. The liquid crystal monomers of claim 1 herein said monomers comprise acryloyloxy groups at each end comprising a terminal carbon—carbon double bond, wherein at least one of said terminal carbon—carbon double bonds is reacted with hydrochloric acid.
 3. Liquid crystal monomers comprising bis(4-(6-methacryloyloxy-A-1-oxy)benzoyl)2-(t-butyl) quinone in which A is selected from the group consisting of a hexyl group, a heptyl group, an octyl group, a nonyl group, a decyl group, or a mixture of such monomers.
 4. The liquid crystal monomers of claim 3 wherein said monomers comprise methacryloyloxy groups at each end comprising a terminal carbon—carbon double bond, wherein at least one of said terminal carbon—carbon double bonds is reacted with hydrochloric acid.
 5. Liquid crystal monomers having, the following general structure:

wherein (CH₂)_(n) is selected from the group consisting of an alkyl group and a methyl-substituted alkyl group, wherein n is a number of carbon atoms in said alkyl group, and n is from about 6 to about 12, R₁ and R₂ are selected from the group consisting of hydrogen and a methyl group; and R₂ is an organic group having a bulk greater than R₁ and R₃, said bulk being adapted to provide sufficient steric hindrance to achieve a nematic state at room temperature while suppressing crystallinity of said liquid crystal monomers at room temperature.
 6. Liquid crystal monomers having the following general structure:

wherein (CH₂)_(n) is selected from the group consisting of an alkyl group and a methyl-substituted alkyl group, wherein n is the number of carbon atoms in said alkyl group, and n is from about 6 to about 12; R₁ and R₃ are selected from the group consisting of hydrogen and a methyl group, and R₂ comprises a branched alkyl group having a bulk greater than R₁ and R₃, said bulk being adapted to provide sufficient steric hindrance to achieve a nematic state at room temperature while suppressing crystallinity of said liquid crystal monomers at room temperature.
 7. The liquid crystal monomers of claim 6 wherein said branched alkyl group is a tertiary butyl group.
 8. The liquid crystal monomers of claim 6 wherein R₂ consists essentially of said alkyl group.
 9. The liquid crystal monomers of claim 7 wherein R₂ consists essentially of said alkyl group.
 10. The liquid crystal monomers of claim 5 comprising terminal carbon—carbon bonds, wherein at least one of said terminal carbon—carbon double bonds is reacted with hydrochloric acid.
 11. The liquid crystal monomers of claim 6 comprising terminal carbon—carbon bonds, wherein at least one of said terminal carbon—carbon double bonds is reacted with hydrochloric acid.
 12. The liquid crystal monomers of claim 7 comprising terminal carbon—carbon bonds, wherein at least one of said terminal carbon—carbon double bonds is reacted with hydrochloric acid.
 13. The liquid crystal monomers of claim 8 comprising terminal unsaturated carbon—carbon bonds, wherein at least one of said terminal unsaturated carbon—carbon bonds is reacted with hydrochloric acid.
 14. The liquid crystal monomers of claim 9 comprising terminal unsaturated carbon—carbon bonds, wherein at least one of said terminal unsaturated carbon—carbon bonds is reacted with hydrochloric acid.
 15. Liquid crystal monomers comprising bis (4-(6-acryloxy-A-1-oxy)benzoyl)2-(t-butyl)quinone in which A comprises an alkyl group having from about 6 to about 12 carbon atoms.
 16. The liquid crystal monomers of claim 15 wherein said bis (4-)(6-acryloxy) groups are terminal groups, and at least one of said terminal groups is a methacryloxy group. 